The present invention relates to an instrument for indirectly determining the moisture of soft tissue on an inner surface of an eyelid of a patient.
Dry eye is recognized as a disturbance of the Lachrymal Functional Unit, a system made up of the lachrymal glands, the ocular surface (cornea, conjunctiva and meibomian glands) and lids. This system further includes the sensory and motor nerves that connect these components.
The dry eye phenomenon may result from inadequate tear production: the lachrymal gland fails to produce sufficient tears to keep the conjunctiva and cornea covered by a complete tear layer. The dry eye phenomenon may also stem from an abnormal tear composition, which causes an overly rapid evaporation of the tears. Thus, while the tear gland produces a sufficient amount of tears, the rate of evaporation is such that the entire surface of the eye cannot be kept covered with a complete layer of tears in various activities or environments.
Various means have been disclosed for diagnosing dry eye, or more generally, the extent of moisture in the outer eye. Schirmer's test determines whether the eye produces enough tears to keep it moist. Paper strips, inserted in an outer region of the eye (typically the lower eyelid), absorb the tear liquid. After several minutes, the amount of liquid absorbed is measured. Based on the amount of liquid absorbed, a determination may be made regarding the dryness of the eye. The diagnostic reliability of Schirmer's test has been the subject of scholarly debate, and many believe that the test may systematically produce false “normal” results.
In-vitro tear osmolarity, which indicates the concentration of salts dissolved in the tear, has long been correlated with dryness of the eye. Since the 1970's, increasing severity of eye dryness has been correlated with increasing in-vitro tear osmolarity (see Farris R L, “Tear osmolarity—a new gold standard?” Adv Exp Med Biol 1994; 350:495-503).
Over the years, various techniques and systems have been developed for removing tear liquid from the eye, and for subjecting the liquid to in-vitro analysis. An exemplary commercial product is the TearLab™ Osmolarity system (see Dr. G. N. Foulks et al., “TearLab™ Osmolarity as a Biomarker for Disease Severity in mild to Moderate Dry Eye Disease”. The system is adapted to measure the osmolarity of human tears for diagnosing dry eye disease. The tear liquid is collected directly from the inferior lateral tear meniscus. A single-use, disposable polycarbonate microchip contains a microchannel at the tip, designed to collect 50 nanoliters (nL) of tear fluid directly from the inferior meniscus of the ocular surface. Gold electrodes embedded in the polycarbonate card enable in-vitro measurement of the electrical impedance of the tear fluid sample in the channel. The measured impedance is correlated to eye dryness, and to measured eye dryness parameters of Schirmer's test and other diagnostic measurement methods for determining dry eye.
Table 1 of Foulks et al., provided as Table 1 hereinbelow, shows typical values for various eye dryness diagnostic methods, as a function of severity—Grade 0 to Grade 4, with Grade 4 representing the highest severity of dry eye disease.
TABLE 1Grade01234Schirmer Test (mm)357520TBUT (seconds)457530Staining (NEI/Industry scale)0381220OSDI0153045100Meibomian Grading Score05122028Osmolarity (mOsms/L)275308324364400It is intuitively evident that in Schirmer's Test, tear absorption length would be expected to decrease with increasing severity of dry eye disease. Table 1 demonstrates this trend. Similarly, it would be expected that the degree of salinity, or osmolarity, of the tear liquid would increase with increasing severity of dry eye disease. Table 1 also demonstrates this trend.
Foulks et al., statistically derive an equation correlating osmolarity and severity of eye dryness. On a scale of 0 to 1 (where 1 represents the highest level of severity), the correlation equation is given as:SEVERITY=(y−275)/125where y is the osmolarity in units of mOsms/L. It is clear from Table 1 and from the correlation equation, that increasing osmolarity is indicative of increasingly severe eye dryness.
U.S. Pat. No. 4,996,993, filed Dec. 7, 1988, discloses several devices for determining in-vivo tear osmolarity in the open eye. A first device, an osmometer, is adapted to measure the osmolarity of a bodily fluid such as tears or sweat, and includes a detachable probe in combination with means for measuring the conductivity between two electrodes of the probe. The osmometer further includes means for converting the measured value of conductivity of the in-vivo sample into a corresponding value of osmolarity and display means for displaying a visible representation of that value.
A second device is adapted to measure, by means of a sensor, some physical quantity (such as dew point temperature) related to the vapor pressure from a bodily fluid. The device is mounted inside a confining, generally concave shell placed adjacent to a portion of the human body for a measurement to be made. To measure tear osmolarity in the open eye, the confining shell could take the form of a conventional eyecup. The sensor can be a thermocouple or thermistor controlled by a microprocessor to measure vapor pressure by the dew point depression method.
U.S. Pat. No. 4,996,993 fails to explicitly disclose the basis for converting the measured value of conductivity of the in-vivo sample into a corresponding value of osmolarity. However, in studying U.S. Pat. No. 4,996,993, one of ordinary skill in the art would appear to derive some guidance from that patent's reference to a relevant journal article, and to the patent's treatment thereof:                The particular pathologic condition designated “dry eye” and its connection to tear film osmolarity is described in the article “Osmolarity of Tear Microvolumes in Keratoconjunctivitis Sicca,” by Jeffrey P. Gilbard et al., in Arch. Ophthalmol., Vol. 96, April, 1978, pages 677-681. When the surface of the eye starts to dry out the tear film becomes hypertonic (elevated osmolarity), causing discomfort and epithelial damage.Thus, although U.S. Pat. No. 4,996,993 fails to provide an explicit relationship between in-vivo measurement of conductivity and tear liquid osmolality, it is fairly understood that higher conductivity (or lower impedance) measurements are correlated with eye dryness, as taught by Gilbard et al., the above-referenced Farris article (which also references and supports the findings of Gilbard), and as confirmed and detailed in the recent study of Foulks et al., referenced above.        
In “Electrical conductivity of tear fluid in healthy persons and keratoconjunctivitis sicca patients measured by a flexible conductimetric sensor” [Graefe's Arch Clin Exp Ophthalmol (1996) 234:542-546], Ogasawara et al. disclose a flexible conductimetric sensor that is small enough and flexible enough to be placed on the ocular surface to measure the electrical conductivity of tear fluid in vivo. The sensitive area of the sensor was placed within the lower temporal conjunctival cul-de-sac. The conductivity was measured continuously for more than 30 seconds. The sodium chloride concentration of tear fluids was calculated from a calibration curve relating electrical conductivity (Siemens) to the NaCl concentration (g/l), and converted to the equivalent electrolyte concentration.
The average electrolyte concentration of 33 samples obtained from 17 healthy persons was 296.4 mEq/l. The electrolyte concentration in 29 samples obtained from keratoconjunctivitis sicca patients averaged 324.8 mEq/l. The difference was found to be statistically significant.
The above-described advances notwithstanding, the present inventor has recognized a need for improved, patient-friendly, cost-effective devices and methods for evaluating the moistness or dryness in the vicinity of the outer eye, and the subject matter of the present disclosure and claims is aimed at fulfilling this need.